Uric Acid in Cardiovascular Diseases: A Factor or an Incident? (original) (raw)

THE ROLE OF URIC ACID IN CARDIOVASCULAR DISEASE AND ITS CLINICAL IMPLICATIONS

2004

A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardiovascular and renal diseases especially in patients with diabetes mellitus, hypertension or heart failure. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Moreover patients with hypertension and hyperuricemia have a 3-to 5-fold increased risk of experiencing coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels.Although the mechanisms by which uric acid may playa pathogenetic role in cardiovascular disease is unclear, hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemorheology, and aggregation. Xanthine oxidase inhibitors (e.g., allopurinol) or a variety of uricosuric agents (e.g., probenecid, sulfinpyrazone,benzbromarone,and benziodarone) can lower elevated uric acid levels but it is unknown whether these agents reversibly impact cardiovascular outcomes. Overall, serum uric acid may be a powerful tool to help stratify risk for cardiovascular disease. At the very least, it should be carefully considered when evaluating overall cardiovascular risk.

The role of uric acid in the pathogenesis of human cardiovascular disease

Heart, 2013

Hyperuricaemia is common in subjects with cardiovascular disease, but is not commonly considered a true risk factor. Recent studies suggest that uric acid is biologically active and can stimulate oxidative stress, endothelial dysfunction, inflammation and vasoconstriction. Epidemiological studies have found that uric acid can independently predict the development of hypertension, as well as stroke and heart failure. Experimentally raising uric acid in animals increases blood pressure, and pilot studies suggest that lowering uric acid in humans can reduce blood pressure in hypertensive individuals. Uric acid may also have emerging roles in the pathogenesis of kidney disease, metabolic syndrome and diabetes. More studies need to be performed on the pathophysiology and clinical consequences of hyperuricaemia in cardiovascular disease.

Uric acid: from a biological advantage to a potential danger. A focus on cardiovascular effects

Vascular Pharmacology, 2019

Non-communicable diseases represent nowadays the most common cause of death worldwide, having largely overcome infectious diseases. Among them, cardiovascular diseases constitute the majority. Given these premise, great efforts have been made by scientific societies to emphasize the fundamental role of cardiovascular prevention and risk factors control. In addition to classical cardiovascular risk factors such as smoking, arterial hypertension, hypercholesterolemia and male gender, new risk factors are emerging from international literature. Among them, uric acid is the protagonist. Several evidences show a direct role of hyperuricemia in the determinism of metabolic and vascular disorders. From the other hand, some researchers have demonstrated that uric ac id is only a marker of cardiovascular damage and not a risk factor for its development. Aim of this review is to evaluate the scientific evidences on the role of uric acid in cardiovascular diseases in order to shed light on this confusing topic.

The Role of Uric Acid in Acute and Chronic Coronary Syndromes

Journal of Clinical Medicine, 2021

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA’s relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while...

Serum Uric Acid And Cardiovascular Disease.

A substantial body of epidemiological and experimental evidence suggests the significance of serum uric acid as an important and independent risk factor of cardiovascular and renal diseases especially in patients with diabetes mellitus, hypertension or heart failure. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Moreover patients with hypertension and hyperuricemia have a 3- to 5-fold increased risk of experiencing coronary artery disease or cerebrovascular disease compared with patients with normal uric acid levels. Although the mechanisms by which uric acid may play pathogenetic role in cardiovascular disease is unclear. Hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemorheology, and aggregation. Xanthine oxidase inhibitors (e.g., allopurinol) or a variety of uricosuric agents (e.g., probenecid, sulfinpyrazone, benzbromarone, and benziodarone) can lower elevated uric acid levels but it is unknown whether these agents reversibly impact cardiovascular outcomes. Hyperuricemia will become then a meaningful target for the prevention and treatment of cardiovascular disease. Overall, serum uric acid may be a powerful tool to help stratify risk for cardiovascular disease. At the very least, it should be carefully considered when evaluating overall cardiovascular risk. KEYWORDS: Hypertension; uric acid; gout; allopurinol; coronary heart disease.

Uric Acid and Cardiovascular Disease: An Update

European Cardiology Review, 2016

In recent years, serum uric acid (SUA) as a determinant of cardiovascular (CV) risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia SUA are at increased risk of cardiac, renal and vascular damage and CV events. There is now some evidence to suggest that urate-lowering treatment may reduce CV risk in this group and, thus, may represent a new strategy in risk reduction.

Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?

Hypertension, 2003

Hyperuricemia is associated with hypertension, vascular disease, renal disease, and cardiovascular events. In this report, we review the epidemiologic evidence and potential mechanisms for this association. We also summarize experimental studies that demonstrate that uric acid is not inert but may have both beneficial functions (acting as an antioxidant) as well as detrimental actions (to stimulate vascular smooth muscle cell proliferation and induce endothelial dysfunction). A recently developed experimental model of mild hyperuricemia also provides the first provocative evidence that uric acid may have a pathogenic role in the development of hypertension, vascular disease, and renal disease. Thus, it is time to reevaluate the role of uric acid as a risk factor for cardiovascular disease and hypertension and to design human studies to address this controversy.

Uric Acid and Oxidative Stress

Current Pharmaceutical Design, 2005

U'c acid is the final product of purine metabolism in humans. The final two reactions of its production catalyzingthe conversion ofhypoxanthineto xanthine and the latter.to uric.acid are catalysed by the enzyme xanthine oxidoreductme, which may attaln tlvo rnter-convertible forms, namely xanthine dehydrogenase or xanthine oxidase The latter uses molecular oxygen as electron acceptor and generates superoxide anion and other reactive oxygen products The role of uric acid in conditions associated with o;idative stress is not entirely clear. Evidence mainly based on epidemiotogical studies suggests that increased serum levels of uric acid are a risk factor for cardiovascular disease where oxidative stress plays an important pathophysiological role. Also, allopurinol, a xanthine oxidoreductase inhibitor that lowers serum levels of uric acid exerts protective;ffects in situations associated with oxidative stress (e g ischaemiareperfusion in1ury, cardiovascular disease). However, there is increasing experimental and clinical evidence showing that uric acid has an important role in vivo as an antioxidant'

Uric acid and oxidative stress: Relative impact on cardiovascular risk

Nutrition, Metabolism and Cardiovascular Diseases, 2007

Post-hoc analyses of the GREACE and the LIFE trials have renewed the interest in elevated serum uric acid (SUA) as a factor contributing to atherosclerotic cardiovascular disease (CVD) and in the possible benefit derived from its pharmacological reduction. The results of these trials are consistent with reports indicating favourable effects of SUA lowering treatment with allopurinol on the rate of cardiovascular complications in patients with coronary heart disease, congestive heart failure and dilated cardiomyopathy.

Allopurinol, uric acid, and oxidative stress in cardiorenal disease

International Urology and Nephrology, 2011

In humans, the hepatic end product of purine metabolism is uric acid. Serum uric acid levels physiologically and gradually rise during human lifetime. Hyperuricemia also arises from excess dietary purine or ethanol intake, decreased renal excretion of uric acid, tumor lysis in lymphoma, leukemia or solid tumors, and sometimes pharmacotherapy. The definition of hyperuricemia is currently arbitrary. Hyperuricemia is associated with chronic kidney disease, arterial hypertension, coronary artery and heart disease, cerebrovascular disease and diabetes mellitus. Xanthine oxidase, a hepatic enzyme, catalyzes the production of uric acid, nitric oxide, and reactive oxygen species, which potentially damage deoxyribonucleic acid, ribonucleic acid and proteins, inactivate enzymes, oxidize amino acids and convert polyunsaturated fatty acids to lipids. This is believed to contribute to atherosclerosis, endothelial dysfunction, renovascular hypertension, and cardiovascular disease. Xanthine oxidase inhibition efficiently blocks uric acid generation, and this improves glomerular filtration rates, systemic blood pressure, and cerebrocardiovascular outcomes. Here, data from animal, in vivo, retro-and prospective, and interventional studies are reported.